The new combination highly active antiretroviral therapies (HAART) for HIV infection have greatly improved the prognosis for HIV infected patients capable of tolerating these regimens. In the absence of such therapy, the ultimate failure of the immune response leads to death in the great majority of patients. However, despite dramatic suppression of viral replication, the extent of immunologic re-constitution achieved following HAART appears to be limited. Thalidomide is a potent immune response modulating drug with an incompletely understood mechanism of action. Our recent studies both in HIV infected patients and in vitro, have revealed novel immunostimulatory properties of thalidomide. The drug acts as a costimulator of primary T cells in vitro, and causes increases in T cell activation and Interleukin-12 (IL-12) production in vivo. The present study seeks to explore the possibility that thalidomide treatment of patients receiving HAART may enhance functional immunity. We plan to evaluate the effect of thalidomide administration to a cohort of such patients on cellular and humoral responses to two vaccines: keyhole limpet hemocyanin (a neoantigen) and polyvalent pneumococcal polysaccharide (a type 2 T cell independent antigen). In addition, the possible impact of immune stimulation by thalidomide and/or vaccination on HIV replication in patients receiving HAART will be evaluated.